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COmparison of the Pharmacodynamics and Pharmacokinetics Ticagrelor Versus Clopidogrel in Patients With CKD and NSTE-ACS (OPT-CKD)

Primary Purpose

Non ST Segment Elevation Acute Coronary Syndrome, Chronic Kidney Disease

Status

Unknown status

Phase

Phase 4

Locations

China

Study Type

Interventional

Intervention

Ticagrelor

Clopidogrel

About this trial

This is an interventional treatment trial for Non ST Segment Elevation Acute Coronary Syndrome focused on measuring Ticagrelor, Pharmacokinetics, NSTE-ACS, CKD

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

P2Y12 inhibitor naïve patients presenting with NSTE-ACS (unstable angina or non-ST segment elevation myocardial infarction).
Males and non-pregnant females > 18 years of age.
eGFR<60 ml/min/1.73m2 (MRDR formula).
With planned percutaneous coronary intervention(PCI will be performed over 24 hours after loading dose).
Written informed consent provided.Provision of informed consent prior to any study specific procedures.

Exclusion Criteria:

Cardiogenic shock.
Thrombolytic therapy administered before randomization.
Active bleeding or bleeding predisposition, including the retinal or vitreous hemorrhage , gastrointestinal or urinary tract hemorrhage , history of intracranial haemorrhage or cerebral infarction .
Hypersensitivity to ticagrelor or any excipients.
Deep puncture or major surgery within 1 month.
Untreated or uncontrolled hypertension with blood pressure >180/110 mmHg.
Known hemoglobin <10 g/dL or platelet count <100 × 109/L.
Known moderate or severe hepatic impairment.
Known aminotransferase level >3x the upper limit of normal.
Known allergy to any of the study drugs or devices (aspirin, clopidogrel, ticagrelor stainless steel, contrast agents, etc.).
Pregnancy or lactation.
Any condition which might interfere with study compliance, or otherwise unsuitable for study participation as judged by the investigators.
Unwilling or unable to get repeat platelet assay or clinical follow-up.
Unwilling or unable to provide written informed consent.

Sites / Locations

Shenyang Northern HospitalRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Ticagrelor group

Clopidogrel group

Arm Description

ticagrelor 180mg loading, followed by 90mg bid for 30 days

clopidogrel 600mg loading, followed by 75mg/d for 30 days

Outcomes

Primary Outcome Measures

PRU assayed by VerifyNow

Secondary Outcome Measures

PRU assayed by VerifyNow

Index of Platelet activity

calculated by the change of the P2Y12 reaction units (PRU) from baseline

Rate of high on-treatment platelet reactivity (HPR)

Plasma concentration of ticagrelor and clopidogrel

Bleeding events

by BARC classification

Full Information

NCT ID

NCT02578537

First Posted

October 15, 2015

Last Updated

December 10, 2015

Sponsor

Shenyang Northern Hospital

1. Study Identification

Unique Protocol Identification Number

NCT02578537

Brief Title

COmparison of the Pharmacodynamics and Pharmacokinetics Ticagrelor Versus Clopidogrel in Patients With CKD and NSTE-ACS

Acronym

OPT-CKD

Official Title

COmparison of the Pharmacodynamics and Pharmacokinetics of Ticagrelor Versus Clopidogrel in Patients With Chronic Kidney Disease and Non-ST-Elevation Acute Coronary Syndromes(OPT-CKD Trial)

Study Type

Interventional

2. Study Status

Record Verification Date

December 2015

Overall Recruitment Status

Unknown status

Study Start Date

October 2015 (undefined)

Primary Completion Date

April 2016 (Anticipated)

Study Completion Date

July 2016 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Shenyang Northern Hospital

4. Oversight

Data Monitoring Committee

5. Study Description

Brief Summary

Ticagrelor, a new P2Y12 receptor antagonist, achieve faster, consistent and higher platelet inhibition than clopidogrel, which was considered more noticeable in patients with ACS combining chronic kidney disease(CKD). Nonetheless, the pharmacokinetic properties of ticagrelor in the patients with CKD and NSTE-ACS has not been thoroughly studied. This study was designed to provide PK and PD data of ticagrelor compared with clopidogrel, in order to estimate that ticagrelor is superior to clopidogrel in getting better inhibition of platelet in patients with CKD and NSTE-ACS. P2Y12 inhibitor naïve patients with CKD (eGFR < 60 ml/min/1.73m2 ) and NSTE-ACS will be enrolled in this single-center, prospective, randomized, parallel-control study and randomly assigned in a one-to-one ratio to receive ticagrelor or clopidogrel on top of chronic aspirin treatment. The primary endpoint was the PRU by Verify Now at 30 days after loading dose.

Detailed Description

Dual antiplatelet therapy with aspirin and clopidogrel has become the standard care in patients with acute coronary syndrome (ACS). However, clopidogrel is being questioned for its insufficient platelet inhibition and residual platelet reactivity, especially in patients with impaired renal function. Ticagrelor, a new P2Y12 receptor antagonist, achieve faster, consistent and higher platelet inhibition than clopidogrel, which was more noticeable in patients with ACS combining chronic kidney disease(CKD). Nonetheless, the pharmacokinetic properties of ticagrelor in the patients with CKD and NSTE-ACS, to the best of the investigators' knowledge, has not been thoroughly studied. This study was designed to provide PK and PD data of ticagrelor compared with clopidogrel, in order to estimate that ticagrelor is superior to clopidogrel in getting better inhibition of platelet in patients with CKD and NSTE-ACS. The potential hypothesis is to evaluate the correlation of platelet inhibition and renal function and CYP2C19 gene type in patients treated by ticagrelor and clopidogrel. P2Y12 inhibitor naïve patients with CKD (eGFR < 60 ml/min/1.73m2 ) and NSTE-ACS will be enrolled in this single-center, prospective, randomized, parallel study and randomly assigned in a one-to-one ratio to receive ticagrelor or clopidogrel on top of chronic aspirin treatment. The primary endpoint was the PRU by Verify Now at 30 days after loading dose.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Non ST Segment Elevation Acute Coronary Syndrome, Chronic Kidney Disease

Keywords

Ticagrelor, Pharmacokinetics, NSTE-ACS, CKD

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 4

Interventional Study Model

Parallel Assignment

Masking

Outcomes Assessor

Allocation

Randomized

Enrollment

60 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Ticagrelor group

Arm Type

Experimental

Arm Description

ticagrelor 180mg loading, followed by 90mg bid for 30 days

Arm Title

Clopidogrel group

Arm Type

Active Comparator

Arm Description

clopidogrel 600mg loading, followed by 75mg/d for 30 days

Intervention Type

Drug

Intervention Name(s)

Ticagrelor

Other Intervention Name(s)

Brilinta

Intervention Description

Ticagrelor group:all patients receive ticagrelor (180 mg loading dose, then 90 mg twice daily followed for 30 days). All patients were given aspirin 100 mg per day unless they were intolerant. For those not previously given aspirin, a loading dose of 300 mg was preferred.

Intervention Type

Drug

Intervention Name(s)

Clopidogrel

Other Intervention Name(s)

Plavix

Intervention Description

Clopidogrel group:all patients receive clopidogrel (600 mg loading dose, then 75 mg once daily followed for 30 days). All patients were given aspirin 100 mg per day unless they were intolerant. For those not previously given aspirin, a loading dose of 300 mg was preferred.

Primary Outcome Measure Information:

Title

PRU assayed by VerifyNow

Time Frame

30 days after loading does of study drug

Secondary Outcome Measure Information:

Title

PRU assayed by VerifyNow

Time Frame

at the time of pre-dose, and 2 hours, 8 hours, and 24 hours after loading dose of study durg.

Title

Index of Platelet activity

Description

calculated by the change of the P2Y12 reaction units (PRU) from baseline

Time Frame

at the time of 2 hours, 8 hours, and 24 hours after loading dose of study drug

Title

Rate of high on-treatment platelet reactivity (HPR)

Time Frame

at the time of pre-dose, and 2 hours, 8 hours, 24 hours and 30 days after loading dose of study durg.

Title

Plasma concentration of ticagrelor and clopidogrel

Time Frame

at 2 hours, 8 hours, and 24 hours after loading dose of study durg.

Title

Bleeding events

Description

by BARC classification

Time Frame

30 days after loading does of study drug

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: P2Y12 inhibitor naïve patients presenting with NSTE-ACS (unstable angina or non-ST segment elevation myocardial infarction). Males and non-pregnant females > 18 years of age. eGFR<60 ml/min/1.73m2 (MRDR formula). With planned percutaneous coronary intervention(PCI will be performed over 24 hours after loading dose). Written informed consent provided.Provision of informed consent prior to any study specific procedures. Exclusion Criteria: Cardiogenic shock. Thrombolytic therapy administered before randomization. Active bleeding or bleeding predisposition, including the retinal or vitreous hemorrhage , gastrointestinal or urinary tract hemorrhage , history of intracranial haemorrhage or cerebral infarction . Hypersensitivity to ticagrelor or any excipients. Deep puncture or major surgery within 1 month. Untreated or uncontrolled hypertension with blood pressure >180/110 mmHg. Known hemoglobin <10 g/dL or platelet count <100 × 109/L. Known moderate or severe hepatic impairment. Known aminotransferase level >3x the upper limit of normal. Known allergy to any of the study drugs or devices (aspirin, clopidogrel, ticagrelor stainless steel, contrast agents, etc.). Pregnancy or lactation. Any condition which might interfere with study compliance, or otherwise unsuitable for study participation as judged by the investigators. Unwilling or unable to get repeat platelet assay or clinical follow-up. Unwilling or unable to provide written informed consent.

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Heyang Wang, MD

Phone

86-024-28897309

whysmmu@163.com

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Yaling Han, MD

Organizational Affiliation

General Hospital of Shenyang Military Region

Official's Role

Principal Investigator

Facility Information:

Facility Name

Shenyang Northern Hospital

City

Shenyang

State/Province

Liaoning

ZIP/Postal Code

110016

Country

China

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Yaling Han, MD,PHD

Phone

86-024-28856123

hanyaling@263.net

First Name & Middle Initial & Last Name & Degree

Yi Li, MD

Phone

86-024-28897309

doctorliyi@126.com

12. IPD Sharing Statement

Citations:

PubMed Identifier

35224730

Citation

Natale P, Palmer SC, Saglimbene VM, Ruospo M, Razavian M, Craig JC, Jardine MJ, Webster AC, Strippoli GF. Antiplatelet agents for chronic kidney disease. Cochrane Database Syst Rev. 2022 Feb 28;2(2):CD008834. doi: 10.1002/14651858.CD008834.pub4.

Results Reference

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COmparison of the Pharmacodynamics and Pharmacokinetics Ticagrelor Versus Clopidogrel in Patients With CKD and NSTE-ACS

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